Infliximab for the Prevention of Recurrent Crohn's Disease After Surgery

NCT00688636 | Completed Phase 4 Results DMC

• 1 other identifier: C0168X75
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, placebo-controlled pilot study to determine endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or ileocolonic surgery in patients receiving post-operative infliximab or placebo

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• Endoscopic Recurrence: the Proportion of Patients in Endoscopic Recurrence at One Year

  Endoscopic recurrence was defined as i2,i3,i4. We used the Rutgeerts' Endoscopic Scoring System. Scores as follows i0, no lesions; i1, 5 or fewer aphthous lesions; i2, more than 5 aphthous lesions with normal mucosa between the lesions or skip areas of larger lesions or lesions confined to the ileocolonic anastomosis; i3, diffuse, aphthous ileitis with diffusely inflamed mucosa; and i4, diffuse inflammation with large ulcers, nodules, and/or narrowing. Endoscopic recurrence was defined as i2,i3,i4 and endoscopic remission was defined as i0 or i1.

  one year

Secondary Outcomes (4)

• Clinical Recurrence at One Year: Defined by Crohn's Disease Activity Index (CDAI) > 200

  One year

• Histological Recurrence of Crohn's Disease as Determined From Biopsies of Neo-terminal Ileum Above the Ileocolonic Anastomosis

  One year

• C-reactive Protein Concentration as a Surrogate Marker of Inflammation

  one year

• Mean Erythrocyte Sedimentation Rate

  one year

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: infliximab

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

infliximab DRUG

5 mg/kg IV at baseline, 2 weeks, 6 weeks and then every 8 weeks x 6

Also known as: Remicade

1

placebo DRUG

placebo IV at baseline, 2 weeks, 6 weeks and then every 8 weeks x 6

2

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men/women \> 18 years of age
• curative resection/ileocolonic anastomosis for Crohn's disease
• may have received previously received infliximab
• if on oral aminosalicylates or corticosteroids, dose must be stable for 4 weeks prior to surgery
• if on 6-mercaptopurine,azathioprine or methotrexate,individual must have been on it for minimum of 3 months prior to surgery with stable dose for 4 weeks
• men and women must use adequate birth control for duration of study and for 6 months after receiving the last infusion
• antibiotics for treatment of Crohn's disease must be discontinued within 12 weeks after surgery; antibiotics are allowable throughout study as long as primary purpose of antibiotic therapy is not for primary treatment of Crohn's disease
• screening lab results must meet screening criteria (hemoglobin = or \> 8.5g/dL; Serum glutamic oxaloacetic transaminase ,3 times upper normal limit,platelets =or\> 100 x 10 9th/L; lymphocytes count =or\> 0.5 x 10 9th/L and neutrophils =or\> 1.0 x 10 9th/L
• have a documented negative reaction to a purified protein derivative skin test performed within 3 months prior to baseline
• have a normal chest radiograph results within 3 months prior to baseline
• are capable of providing written informed consent and obtained prior to conducting any protocol-specified procedures
• willing to adhere to the study visit schedule and other protocol requirements
• are considered eligible according to the tuberculosis eligibility assessment, screening and early detection of reactivation rules
• patients who undergo resective surgery and primary ileocolonic anastomosis with a temporary ileostomy upon takedown of the diverting ileostomy.

You may not qualify if:

• patients with greater than 10 years of Crohn's disease requiring first resection of a short (\<10cm) fibrostenotic stricture
• macroscopically active disease at anastomosis at time of surgery
• presence of stoma
• prior severe infusion reaction to infliximab
• history of anaphylaxis to murine products or other chimeric proteins
• any of the following medications taken within 12 weeks of surgery: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, investigational drugs, or medications targeted at reducing tumor necrosis factor
• have a positive stool culture for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin and have clinically significant signs of an enteric infection at screening
• women who are pregnant, nursing or planning pregnancy during the trial or within 6 months after the last infusion
• patient with active tuberculosis, patient newly diagnosed with latent tuberculosis who's receiving tuberculosis prophylaxis, patient with recent close contact to individual with active tuberculosis
• have or have had opportunistic infection within 6 months of screening
• have chest radiograph within 3 months prior to screening that shows malignancy, infection, or abnormalities suggestive of tuberculosis
• documentation of seropositive for HIV
• documentation of a positive test for hepatitis B surface antigen or a history of documented hepatitis C
• have current signs/symptoms of systemic lupus erythematosus, or severe progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral diseases
• presence of a transplanted solid organ (with exception of corneal transplant \> 3 months prior to randomization)

Sponsors & Collaborators

• University of Pittsburgh: lead
• Centocor, Inc.: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (1)

• Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology. 2009 Feb;136(2):441-50.e1; quiz 716. doi: 10.1053/j.gastro.2008.10.051. Epub 2008 Oct 31.

  PMID: 19109962 RESULT

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Limitations to our study included a small sample size, a disproportionate number of smokers in the infliximab group, more patients on immunomodulators in the placebo group, and inclusion of patients who had previously received infliximab.

Results Point of Contact

• Title: Research Coordinator
• Organization: Univerisity of Pittsburgh

goldbyreffnerka@upmc.edu

412-648-9173

Study Officials

• Miguel D Regueiro, M.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: June 3, 2008
• Study Start: January 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: January 1, 2009
• Last Updated: September 26, 2016
• Results First Posted: September 26, 2016

Record last verified: 2016-09

Locations

US (1)